       Document 0246
 DOCN  M9610246
 TI    Regulation of interleukin 12 p40 expression through an NF-kappa B
       half-site.
 DT    9601
 AU    Murphy TL; Cleveland MG; Kulesza P; Magram J; Murphy KM; Department of
       Pathology, Washington University School of; Medicine, St. Louis,
       Missouri 63110, USA.
 SO    Mol Cell Biol. 1995 Oct;15(10):5258-67. Unique Identifier : AIDSLINE
       MED/96009550
 AB    Interleukin 12 (IL-12) is an inducible cytokine composed of 35- and
       40-kDa subunits that is critical for promoting T helper type 1
       development and cell-mediated immunity against pathogens. The 40-kDa
       subunit, expressed by activated macrophages and B cells, is induced by
       several pathogens in vivo and in vitro and is augmented or inhibited by
       gamma interferon (IFN-gamma) or IL-10, respectively. Control of IL-12
       p40 expression is therefore important for understanding resistance and
       susceptibility to a variety of pathogens, including Leishmania major and
       perhaps human immunodeficiency virus. In this report, we provide the
       first characterization of IL-12 p40 gene regulation in macrophages. We
       localize inducible activity of the promoter to the sequence
       -122GGGGAATTTTA-132 not previously recognized to bind Rel family
       transcription factors. We demonstrate binding of this sequence to
       NF-kappa B (p50/p65 and p50/c-Rel) complexes in macrophages activated by
       several p40-inducing pathogens and provide functional data to support a
       role for NF-kappa B family members in IL-12 p40 activation. Finally, we
       find that IFN-gamma treatment of cells enhances this binding
       interaction, thus potentially providing a mechanism for IFN-gamma
       augmentation of IL-12 production by macrophages.
 DE    Animal  Base Sequence  Cells, Cultured  DNA/METABOLISM  *Gene Expression
       Regulation/DRUG EFFECTS  Genes, Structural/*GENETICS  Human  Interferon
       Type II/PHARMACOLOGY  Interleukin-12/*GENETICS
       Lipopolysaccharides/PHARMACOLOGY  Macrophage Activation  Macrophages,
       Peritoneal  Mice  Molecular Sequence Data  NF-kappa B/*METABOLISM
       Promoter Regions (Genetics)/*GENETICS  Proto-Oncogene
       Proteins/METABOLISM  Recombinant Fusion Proteins/BIOSYNTHESIS  Sequence
       Deletion  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Transcription Factors/METABOLISM  Transcription, Genetic  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

